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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 307 records · Page 17Linked to original sources
PubMed1992

Therapeutic effect of oral dipyridamole on myocardial perfusion and cardiac performance in patients with hypertrophic cardiomyopathy.

Recent studies have indicated that myocardial ischemia could occur and could play an important role in the pathophysiology of patients with hypertrophic cardiomyopathy (HCM). We therefore investigated whether or not dipyridamole--a selective coronary vasodilating agent--could favorably modify myocardial perfusion and the clinical manifestations in 20 patients with HCM (19 nonobstructive and one mildly obstructive) with an average age of 50 years. Oral dipyridamole, 150 mg/day for 2 weeks, prevented reversible perfusion defects initially observed in six patients on baseline exercise thallium-201 (201TI) scintigraphy and significantly increased the 201TI clearance (40 +/- 13% to 44 +/- 12%), while one patient developed new reversible perfusion defects. There were significant increases in echocardiographic fractional shortening and treadmill exercise time and reductions in cardiac size and supraventricular arrhythmias with dipyridamole therapy. These observations suggest that coronary vasodilation with dipyridamole may improve myocardial perfusion and cardiac function in patients with HCM.

Administration, Oral↗
PubMed1992

Use of single strand conformation polymorphism analysis to detect point mutations in human mitochondrial DNA.

Myoclonus epilepsy with ragged-red fibers (MERRF) has been shown to be associated with a specific point mutation at the nucleotide 8344 in the tRNA(Lys) gene of mitochondrial DNA (mtDNA). We screened 6 patients with clinically diagnosed MERRF and 1 patient with ocular myopathy for point mutations in the tRNA(Lys) gene, using single strand conformation polymorphism (SSCP) analysis, which can detect even a 1-basepair difference between 2 DNA sequences. Using SSCP and consequent DNA sequencing, we identified the known MERRF mutation in 4 out of 6 MERRF patients, as well as in 1 patient with a new clinical phenotype associated with this mutation: progressive external ophthalmoplegia, muscle weakness and a lipoma, but no myoclonus or epilepsy. Two of the patients with clinical MERRF had neither the MERRF-mutation nor any other mutations in the tRNA(Lys) gene. Using SSCP analysis, we also detected a new polymorphism in 1 patient. Thus, SSCP analysis can be applied to search effectively and rapidly for point mutations or polymorphisms in mitochondrial DNA.

Adolescent↗
PubMed1992

HIV-1 gene rev responsible for accumulated heterodisperse RNAs seen in infected T-cells.

To analyze which gene of HIV-1 was responsible for the high accumulation of "heterodisperse RNAs" in virally infected T-cells, Northern blot analysis was performed. Total RNA from inducible cell lines expressing the envelope protein of HIV-1, or the regulatory gene rev, were blotted and hybridized with an Alu probe that detects heterodisperse RNAs. Results show that the rev gene is responsible for the accumulation of cellular heterodisperse RNAs seen earlier in HIV-1-infected T-cells.

Blotting, Northern↗
PubMed1992

Comparison of the relaxant effects of diazepam, flunitrazepam and midazolam on airway smooth muscle.

The mechanisms by which benzodiazepines produce muscle relaxation and respiratory depression are not known, but they may include actions on peripheral benzodiazepine receptors or central GABA receptors, or a direct action on airway smooth muscle may also be involved. We have compared, therefore, the effects of diazepam, flunitrazepam and midazolam on airway tone by measuring isometric tension of guineapig trachealis muscle. Cumulative concentrations of diazepam, flunitrazepam and midazolam caused concentration-dependent relaxation of resting tone in the tracheal smooth muscle with no significant differences in pD2 values (-log EC50--an index of potency) or intrinsic activities (% of maximum response) for relaxations for the three compounds. Pretreatment with propranolol 10(-6) mol litre-1, flumazenil 10(-7) and 10(-6) mol litre-1 or PK11195 10(-6) mol litre-1 had no effect on diazepam- or midazolam-induced relaxation. Diazepam 3 x 10(-6) mol litre-1 pretreatment shifted the concentration-response curves for acetylcholine, histamine and serotonin (5-HT) to the right by a factor of approximately 2. Flunitrazepam 3 x 10(-6) mol litre-1 pretreatment also shifted the curves for histamine and 5-HT similarly to the right, whereas midazolam pretreatment did not inhibit any agonist-induced contractions. These results suggest that benzodiazepines relax airway smooth muscle, not via neural pathways or central and peripheral benzodiazepine receptors, but by a direct action on airway smooth muscle.

Animals↗
PubMed1992

The effect of p56lck, a lymphocyte specific protein tyrosine kinase, on the syncytium formation induced by human immunodeficiency virus envelope glycoprotein.

A human CD4+ T cell line, Jurkat, was transfected with a constructed plasmid, which has the envelope gene of the human immunodeficiency virus (HIV) under the transcriptional control of the human metallothionein IIA promoter, and these transfected cells were then cloned. JME2, one of the cloned cell lines, expressing the envelope glycoprotein after induction with metal ions, showed the ability to form syncytia involving other CD4+ cells not expressing the HIV envelope protein. When several CD4+ cell lines were examined for their susceptibility to syncytium formation by JME2 cells, the p56lck-expressing cell lines were found to be more susceptible to syncytium formation than the p56lck-non-expressing cell lines. To substantiate the role of p56lck in the syncytium formation, a CD4+, p56lck-non-expressing monocytoid cell line, U937 clone 2, was transfected with an lck-expressing construct. Using such transfectant cell clones, it was demonstrated that p56lck-positive cells are markedly more susceptible to the syncytium formation than p56lck-negative cells, implying a regulatory role for p56lck in syncytium formation mediated by the HIV envelope and CD4 molecule. Moreover, it was suggested, in the experiments using CD45 cross-linking or a protein tyrosine kinase inhibitor, genistein, that p56lck affects syncytium formation through its protein tyrosine kinase activity. A putative mechanism by which p56lck affects the syncytium formation is also discussed.

CD4 Antigens↗
PubMed1992

Hyperbaric oxygen therapy accelerates neurologic recovery after 15-minute complete global cerebral ischemia in dogs.

BACKGROUND AND METHODS: Although hyperbaric oxygen therapy is clinically used for the treatment of several types of ischemic brain injury, few basic animal studies are available that provide a rationale for this therapy for complete global brain ischemia. Therefore, we investigated the effect of hyperbaric oxygen therapy on neurologic recovery after 15-min complete global cerebral ischemia in a canine model. Complete global ischemia was induced in 19 dogs by occlusion of the ascending aorta and the caval veins. Nine dogs were randomized to treatment with hyperbaric oxygenation (3 atmospheres absolute, 100% oxygen for 1 hr) at 3, 24, and 29 hrs after ischemia under spontaneous respiration, while the other ten dogs served as the control group without hyperbaric oxygen therapy (group C). Neurologic recovery was evaluated based on the electroencephalogram (EEG) activity score (1 = normal; 5 = isoelectric) and the neurologic recovery score (100 = normal; 0 = brain death) over a 14-day postischemic period. RESULTS: The survival rates were 3/10 (30%) in the control group vs. 7/9 (78%) in the group treated with hyperbaric oxygen (p < .05). Over the 14-day postischemic period, the best (lowest) EEG scores of each dog were significantly (1.7 +/- 0.2 vs. 2.9 +/- 0.3; mean +/- SE, p < .01) lower in the hyperbaric oxygen-treated group. The best neurologic recovery scores of each dog were significantly (69 +/- 6 vs. 48 +/- 5; mean +/- SE, p < .05) higher in the treated animals. The number of dogs that recovered to a neurologic recovery score of > 65 (assessed as a slight disability) were 1/10 in the control group and 6/9 in the group treated with hyperbaric oxygen (p < .02). CONCLUSIONS: Hyperbaric oxygen therapy performed in the early postischemic period accelerated neurologic recovery and improved the survival rate in dogs after 15-mins of complete global cerebral ischemia.

Animals↗
PubMed1992

Characterization of three thermophilic strains of Methanothrix ("Methanosaeta") thermophila sp. nov. and rejection of Methanothrix ("Methanosaeta") thermoacetophila.

Three thermophilic Methanothrix ("Methanosaeta") strains, strains PTT (= DSM 6194T) (T = type strain), CALS-1 (= DSM 3870), and Z-517 (= DSM 4774), were characterized chemotaxonomically and compared with five mesophilic strains, Methanothrix soehngenii ("Methanosaeta concilii") GP6 (= DSM 3671), Opfikon (= DSM 2139), FE (= DSM 3013), UA, and PM. These methanogens were exclusively acetotrophic and had a characteristic sheathed structure. The DNA base compositions of the strains which we studied ranged from 50.3 to 54.3 mol% guanine plus cytosine. The thermophilic strains often had phase-refractive gas vesicles inside their cells. Denaturing electrophoresis of proteins showed that the mesophilic and thermophilic Methanothrix strains formed two distinct groups and that there were differences in protein patterns between the groups. The difference between the thermophiles and mesophiles was also verified by comparing partial 16S rRNA sequences (ca. 30 base differences in ca. 540 bases). On the basis of our results, we propose the name Methanothrix thermophila for the three thermophilic strains. The type strain of M. thermophila is strain PT (= DSM 6194). We also propose that the name Methanothrix thermoacetophila ("Methanosaeta thermoacetophila"), which was given to strain Z-517 (type strain), should be rejected because of its description, which was based on an enrichment culture, was inadequate.

Bacterial Proteins↗
PubMed1992

Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.

Cytoplasts from two unrelated patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) harboring an A----G transition at nucleotide position 3243 in the tRNA(Leu(UUR)) gene of the mitochondrial genome were fused with human cells lacking endogenous mitochondrial DNA (mtDNA) (rho 0 cells). Selected cybrid lines, containing less than 15 or greater than or equal to 95% mutated genomes, were examined for differences in genetic, biochemical, and morphological characteristics. Cybrids containing greater than or equal to 95% mutant mtDNA, but not those containing normal mtDNA, exhibited decreases in the rates of synthesis and in the steady-state levels of the mitochondrial translation products. In addition, NADH dehydrogenase subunit 1 (ND 1) exhibited a slightly altered mobility on polyacrylamide gel electrophoresis. The mutation also correlated with a severe respiratory chain deficiency. A small but consistent increase in the steady-state levels of an RNA transcript corresponding to 16S rRNA + tRNA(Leu(UUR)) + ND 1 genes was detected. However, there was no evidence of major errors in processing of the heavy-strand-encoded transcripts or of altered steady-state levels or ratios of mitochondrial rRNAs or mRNAs. These results provide evidence for a direct relationship between the tRNALeu(UUR) mutation and the pathogenesis of this mitochondrial disease.

Acidosis, Lactic↗
PubMed1992

Synthesis and release of interleukin 1 by reoxygenated human mononuclear phagocytes.

To examine the possible involvement of cytokines in reperfusion injury, we have studied production of IL-1 by human vascular cells, including smooth muscle and mononuclear phagocytes. Exposure of cells to hypoxia (pO2 approximately 14 torr) followed by reoxygenation led to significant release of IL-1 only from the mononuclear phagocytes. Elaboration of IL-1 was dependent on the oxygen tension and duration of hypoxia (optimal at lower pO2s, approximately 14-20 torr, and after 9 h), as well as the time in reoxygenation (maximal IL-1 release at 6-9 h). Although a period of hypoxia was necessary for subsequent IL-1 production during reoxygenation of either peripheral blood monocytes or cultured monocyte-derived macrophages, no IL-1 release occurred during the hypoxic exposure. IL-1 released during reoxygenation was newly synthesized, and its production was triggered by the generation of oxygen free radicals, as it could be blocked by the addition of either allopurinol or free radical scavengers to cultures and could be stimulated in part by low concentrations of hydrogen peroxide or xanthine/xanthine oxidase. The potential pathophysiological effects of IL-1-containing supernatants from reoxygenated macrophages was shown by their induction of endothelial tissue factor and enhancement of endothelial adhesiveness for neutrophils, both of which could be blocked by anti-IL-1 antibody. The relevance of IL-1 to hypoxia/reoxygenation in vivo was suggested by the presence of circulating nanogram amounts of this cytokine in the plasma of mice during the reoxygenation period following a hypoxia.

Animals↗
PubMed1992

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): a correlative study of the clinical features and mitochondrial DNA mutation.

We studied 40 MELAS patients (21 male and 19 female) to characterize the clinical features and biochemical and muscle biopsy findings related to the mtDNA mutation at the nucleotide position of 3,243, the most common genetic defect in MELAS. The most frequent symptom was episodic sudden headache with vomiting and convulsions, which commonly affected patients aged 5 to 15 years (80%). Biochemical defects in the muscle were variable; 13 patients had complex I, seven complex IV, and four complexes I + IV deficiencies. In four muscle biopsies without ragged-red fibers or any enzyme defect, we based the diagnosis on the identification of strongly SDH-reactive blood vessels, which occurred in 87.5% of the biopsies. The mtDNA mutation was present in 32 of 40 patients (80%). We conclude that there are no clinical and pathologic differences between the patients with and without this mtDNA mutation.

Acidosis, Lactic↗
PubMed1992

Myocardial energetics and cardiac function of preserved rat heart.

We studied mitochondrial function in relation to ATP production and its relationship with myocardial oxygen consumption (VO2) and total mechanical energy using isolated rat hearts after 8, 12, and 24 h of hypothermic preservation. In isovolumic contraction, ventricular contractility and total mechanical energy were respectively assessed by the end-systolic elastance (Ees) and pressure-volume area (PVA). Ees significantly decreased after hypothermic ischemia, although the difference was not significant between 8 and 12 h. In contrast, VO2 measured at each left ventricular volume increased after hypothermic ischemia. PVA and VO2 were found to stay in linear correlation after prolonged hypothermic ischemia, although VO2 at null PVA and VO2 to PVA ratios significantly increased after hypothermic ischemia, especially after 12-h ischemia. Mitochondrial oxidative phosphorylation significantly decreased after hypothermic ischemia for longer than 12 h. These results indicate that mitochondrial oxidative phosphorylation was impaired due to long time hypothermic ischemia especially after 12-h ischemia. We conclude that energy uncoupling between VO2 and PVA in hypothermically preserved heart is attributable to disturbed mitochondrial oxidative phosphorylation and that 8 h is a critical point for efficient conversion of energy from VO2 into PVA in rat heart.

Animals↗
PubMed1992

Beneficial antiarrhythmic effect of beta-blockade in patients with dilated cardiomyopathy.

Antiarrhythmic effects of beta-blockade (BB) in patients with dilated cardiomyopathy were compared with those of various antiarrhythmic agents using ambulatory Holter monitoring. The BB therapy effectively suppressed ventricular extrasystoles (VEs) in 85% of patients, as evidenced by improvement in Lown's grade or a reduction in the number of the highest grade VEs greater than 50%. In contrast, conventional antiarrhythmic agents, except flecainaid and amiodarone, were poorly effective in suppressing VEs. BB therapy gradually increased left ventricular fractional shortening (16 +/- 6% to 22 +/- 12%) and improved 12-month survival rates as compared with those receiving conventional therapy (93 vs 69%). This antiarrhythmic potency seemed to be an additional therapeutic efficacy of BB in the management of patients with dilated cardiomyopathy, which frequently associated with serious VEs.

Adrenergic beta-Antagonists↗
PubMed1992

Two fatal cases of hepatitis B virus carriers after corticosteroid therapy for bronchial asthma.

We report two hepatitis B virus (HBV) carriers who had liver failure after withdrawal of corticosteroids (steroids) administered for treatment of serious asthmatic attacks. Liver functions deteriorated 1 to 2 wk after withdrawal of the steroid therapy and liver failure occurred. Steroid readministration and intensive therapy for liver failure did not prevent death. An excessive immune response provoked by steroid withdrawal and decreased reserve capacity due to underlying chronic liver disease were thought to be factors in the liver failure. Caution must be exercised in the administration of steroids to patients with underlying chronic HBV infection to prevent exacerbation of hepatitis. Prompt readministration of steroids is indicated if evidence of liver failure develops.

Aged↗
PubMed1992

[Effects of epithelium removal and cooling on tracheal contraction in guinea pigs].

We investigated the effects of epithelium removal and cooling (32 degrees C, 27 degrees C, 22 degrees C) on isolated tracheal smooth muscle contraction induced by bethanechol (BCh), acetylcholine (ACh), histamine (Hist), and KCl in guinea pigs. The pD2 values (-logED50) increased in the epithelium damaged group compared with the intact group when ACh was administered at 37 degrees C, 32 degrees C, 27 degrees C and 22 degrees C, with histamine at all four temperature conditions, and with KCl at 37 degrees C, 32 degrees C and 27 degrees C. In both groups, the pD2 values for BCh, ACh, and KCl tended to decrease as temperature was lowered, and significant decrease in pD2 was observed at 27 degrees C. In contrast, the pD2 value for histamine tended to increase as temperature was lowered in every group. Concerning these agents, we conclude that epithelium removal and cooling exert neither significant nor consistent effect on tracheal epithelial function.

Acetylcholine↗
PubMed1992

[A case of chronic toluene intoxication with atrophy of cerebrum, cerebellum and brainstem on CT and MRI].

A 28-year-old man developed neurological disorders consisting of cerebellar symptoms and dementia over a period of 8 years of inhalation of toluene. He also developed bilateral optic atrophy. CT scan and MRI revealed atrophy of cerebrum, cerebellum and brainstem. The severity of neurological symptoms corresponded with the findings of CT and MRI. Furthermore, MRI (T2) showed reduced signal intensity in bilateral thalamus. This patient was also admitted to another hospital 2.5 years ago. Compared with the previous findings, present examinations showed significant progress of the atrophy of cerebrum and brainstem. It was suggested from the results of ABR that the disturbance of the brainstem was aggravated through this period.

Adult↗